Characterization of Occult Hepatitis B Virus Strains in South African Blood Donors
Characterization of Occult Hepatitis B Virus Strains in South African Blood Donors
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DOI：
10.1002/hep.22879
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发表时间：
2009-06-01
期刊：
影响因子：
13.5
通讯作者：
Candotti, Daniel
中科院分区：
文献类型：
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作者：
Allain, Jean-Pierre;Belkhiri, Dalila;Candotti, Daniel
自2005年10月以来，对在南非采集的所有血液单位进行了人类免疫缺陷病毒（HIV）-1、乙型肝炎病毒和丙型肝炎病毒（HBV、HCV）基因组筛查，发现每种病毒的转化前窗口期（WP）感染和隐匿性HBV感染（OBI），后者定义为持续性HBV DNA，无法检测到B肝炎表面抗原（HBsAg）。通过实时定量聚合酶链反应、巢式扩增、抗-HBc和抗-HBs相结合，确认被鉴定为HBsAg阴性/DNA阳性的样本。对扩增的基本核心启动子/前核心、前S/S和全基因组进行测序、分析，并与73个HBsAg+菌株进行比较。通过系统发育分析确定基因型。在检查的109个样本中，54个被归类为OBI，14个被归类为WP，20个被归类为假阳性，5个被归类为其他分类，16个由于缺乏血清学或随访数据而被归类为未确定。OBI供体主要为男性（67%），中位年龄31岁，黑人（54%），丙氨酸转氨酶水平正常。病毒载量范围为不可定量至518 IU/mL（中位数5 IU/mL）。基因型A1（23株）比基因型D（7株）更常见。基因型A1菌株几乎没有突变。在主要的亲水区，56.5%的菌株为野生型或很少有氨基酸替换。最重要的是，所有13个有趣的基因组序列都存在1到7个已知或假定会对病毒复制产生负面影响的突变。特别是，6/13个序列在HBx基因中具有终止密码子，该终止密码子翻译为117或19-25个C-末端氨基酸的缺失，而在15个HBeAg+ HBsAg+菌株中未发现。一个带有HBx终止密码子的WP序列表明具有感染性。结论：基因型A1 OBI不同于基因型A2和D OBI，因为几乎没有证据表明免疫压力是OBI发生的主要因素。有限的复制似乎主要与遗传病毒缺陷有关。（《肝脏学》2009年;49：1868-1876）
Since October 2005, all blood units collected in South Africa were screened individually for human immunodeficiency virus (HIV)-1, hepatitis B and C virus (HBV, HCV) genomes uncovering preseroconversion window period (WP) infections for each virus and occult HBV infections (OBIs) defined as persistent HBV DNA without detectable hepatitis B surface antigen (HBsAg). Samples identified as HBsAg-negative/DNA-positive were confirmed by combining real-time quantitative polymerase chain reaction, nested amplification, anti-HBc and anti-HBs. Amplified basic core promoter/precore, pre-S/S, and whole genome were sequenced, analyzed, and compared to 73 HBsAg+ strains. Genotype was determined by phylogenetic analysis. From 109 samples examined, 54 were classified as OBI, 14 as WP, 20 as false-positive, five as other classification, and 16 as undetermined due to lack of serological or follow-up data. OBI donors were predominantly males (67%), median age 31 years, black (54%), with normal alanine aminotransferase levels. Viral load ranged between unquantifiable and 518 IU/mL (median 5 IU/mL). Genotype A1 was more frequent (23 strains) than genotype D (seven strains). Genotype A1 strains were little mutated. In the major hydrophilic region, 56.5% strains were wild type or with few amino acid substitutions. Most important, all 13 fun genome sequences presented 1 to 7 mutations known to or assumed to negatively impact viral replication. In particular, 6/13 sequences had a stop codon in the HBx gene translated into deletion of 117 or 19-25 C-terminus amino acids not found in 15 HBeAg+ HBsAg+ strains. One WP sequence with an HBx stop codon suggested infectivity. Conclusion: Genotype A1 OBIs are different from genotype A2 and D OBIs in that there is little evidence of immune pressure as a major factor involved in OBI genesis. Limited replication appears mostly related to genetic viral defects. (HEPATOLOGY 2009;49:1868-1876.)